Department of Neurology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan.
Parkinsonism Relat Disord. 2021 Aug;89:79-83. doi: 10.1016/j.parkreldis.2021.06.026. Epub 2021 Jul 2.
Variants in the low-density lipoprotein receptor-related protein 10 (LRP10), linked to inherited forms of α-synucleinopathies, have been reported. Nine variants of LRP10 were identified in the first such report, and subsequent studies have identified possible pathogenic variants in patients with sporadic Parkinson's disease (PD). Few studies have investigated the role of LRP10 in PD. We sought to validate the role of this gene in Taiwanese patients with PD.
In total, 1277 individuals were included in this study (669 had PD and 608 were controls). The entire LRP10 coding exons and exon-intron boundaries were sequenced in 103 probands with early-onset PD or familial PD. We then genotyped the newly identified variants from the 103 patients and previously reported potential pathogenic variants in our cohort. The frequencies of variants were analyzed.
Five new and possibly pathogenic variants were identified initially. In total, 14 potentially pathogenic variants (including nine previously reported and five newly identified variants) were analyzed thereafter. We did not find any significant associations between any variant and the risk of PD. However, c.1424+5delG was identified in a patient with sporadic PD who was diagnosed as having PD and dementia and who had prominent psychiatric symptoms.
Although we identified a patient with sporadic PD and dementia carrying a c.1424+5delG variant, our data did not provide sufficient evidence to support the role of LRP10 in PD in Taiwanese adults.
载脂蛋白 E 受体相关蛋白 10(LRP10)的变体与α-突触核蛋白病的遗传性形式有关。首次报道中发现了 LRP10 的九个变体,随后的研究在散发性帕金森病(PD)患者中发现了可能的致病性变体。很少有研究调查 LRP10 在 PD 中的作用。我们试图验证该基因在台湾 PD 患者中的作用。
本研究共纳入 1277 名个体(669 名患有 PD,608 名为对照组)。103 名早发性 PD 或家族性 PD 患者的整个 LRP10 编码外显子和外显子-内含子边界进行了测序。然后,我们对 103 名患者中的新发现变体和我们队列中先前报道的潜在致病性变体进行了基因分型。分析了变体的频率。
最初鉴定了五个新的可能致病性变体。总共分析了 14 个潜在致病性变体(包括九个先前报道的和五个新发现的变体)。我们没有发现任何变体与 PD 风险之间存在任何显著关联。然而,在一名被诊断为 PD 和痴呆症且具有明显精神症状的散发性 PD 患者中发现了 c.1424+5delG 突变。
尽管我们鉴定了一名携带 c.1424+5delG 变体的散发性 PD 和痴呆症患者,但我们的数据没有提供足够的证据支持 LRP10 在台湾成年人 PD 中的作用。